The limited diversity of the cotton-top tamarins' (Saguinus oedipus) MHC class I genes is an exception to the high polymorphism and variability displayed by this gene family. Additionally, the cotton-top tamarin MHC class I genes are unusual in that they are related to the human non-classical HLA-G gene. To investigate whether these characteristics are present in other New World primate species we cloned and sequenced MHC class I cDNAs from a saddle-back tamarin (Saguinus fuscicollis), a common marmoset (Callithrix jacchus), a golden-headed lion tamarin (Leontopithecus rosalia), an owl monkey (Aotus trivirgatus), a squirrel monkey (Saimiri sciureus), a saki monkey (Pithecia sp.) and three spider monkeys (Ateles belzebuth). Most of the New World primate MHC class I genes analyzed were related to HLA-G. Interestingly, the New World primate MHC class I genes show an unusual phylogenetic pattern when gene trees of exons 4-8 are constructed. The MHC class I alleles of the Callitrichidae (tamarins and marmosets) are distributed in a species-specific fashion whereas in the non-Callitrichidae New World primates, as in Old World primates, apes and humans, the MHC class I loci are shared by different species. This unusual pattern may indicate that the different Callitrichidae species have different sets of MHC class I loci, suggesting that the MHC class I genes in the Callitrichidae have evolved by repeated cycles of duplication and inactivation (or deletion), that coincide with the adaptive radiation of these species. Additionally, we have isolated one cDNA from the squirrel monkey and another from the saki monkey that have B locus-specific motifs in the 3' half of the coding region. Key Words MHC, Cotton-top tamarin, New World primates, evolution